Body weight remains relatively constant over long periods of time in many animal species. Several decades of research indicate that the central nervous system plays an important role in the precise regulation of food intake and body weight. Recently several hypothses have emerged which attempt to specify the anatomical systems that perform these regulatory functions. The systems on which these hypotheses focus are the catecholamine and indoleamine-containing neurons that originate in the midbrain and pons and terminate extensively in the hypothalamus. In the studies proposed, a comparative approach will be used to examine the role of the monoamines, in particular the catecholamines, in the major animal models of obesity. In normal rats, lesion studies will be used to deplete hypothalamic amines. The relationship of body weight to depletion of amines in discrete areas of the hypothalamus will be studied. In genetically obese rodents, the relationship of spontaneously occurring obesity to monoamine function will be examined. Several types of obese mutants are known to have altered levels of brain or pituitary monoamines. The generality of this finding will be investigated. In addition, the effects on body weight of treatments that alter monoamine levels will be studied. Finally, the effects on monoamine of treatments which alter body weight or suppress food intake will also be examined in these mutants.